Application of nanodiagnostics in point-of-care tests for infectious diseases

Abstract

Although tremendous efforts have been put into the treatment of infectious diseases to prevent epidemics and mortality, it is still one of the major health care issues that have a profound impact on humankind. Therefore, the development of specific, sensitive, accurate, rapid, low-cost, and easy-to-use diagnostic tools is still in urgent demand. Nanodiagnostics, defined as the application of nanotechnology to medical diagnostics, can offer many unique opportunities for more successful and efficient diagnosis and treatment for infectious diseases. In this review, we provide an overview of the nanodiagnostics for infectious diseases from nanoparticle-based, nanodevice-based, and point-of-care test (POCT) platforms. Most importantly, emphasis focused on the recent trends in the nanotechnology-based POCT system. The current state-of-the-art and most promising point-of-care nanodiagnostic technologies, including miniaturized diagnostic magnetic resonance platform, magnetic barcode assay system, cell phone-based polarized light microscopy platform, cell phone-based dongle platform, and paper-based POCT platform, for infectious diseases were fully examined. The limitations, challenges, and future trends of the nanodiagnostics in POCTs for infectious diseases are also discussed.

Keywords: infectious diseases; nanodevices; nanodiagnostics; nanoparticles; pathogens; point-of-care test.

Figure 1

Schematic illustration of the detection of HBsAg using QDNBs for the diagnosis of hepatitis B. Notes: Reprinted by permission from Zhang P, Lu H, Chen J, Han H, Ma W. Simple and sensitive detection of HBsAg by using a quantum dots nanobeads based dot-blot immunoassay. Theranostics. 2014;4(3):307–315. Copyright © 2014 Ivyspring International Publisher. Creative Commons license available at: https://creativecommons.org/licenses/by-nc/4.0/legalcode. Abbreviations: Ab, antibody; EDC, 1-ethyl-3-(3-di-methylaminopropyl) carbodiimide hydrochloride; HBsAg, hepatitis B surface antigen; PVDF, polyvinylidene difluoride; QDs, quantum dots; QDNB, quantum dots nanobead; UV, ultraviolet.

Figure 2

(A) Diagnostic scheme of nanodevice-based detection of blood-borne infectious diseases. (B) Quantum dot barcodes with different color fluorescence image (scale bar =20 µm). (C) Normalized quantum dot emission profiles for the quantum dots used for the barcodes in B. (D) The prototype of the polydimethylsiloxane microfluidic chip. Notes: Reprinted with permission from Klostranec J, Xiang Q, Farcas G, Lee J, Rhee A, Lafferty E, Perrault S, Kain K, Chan W. Convergence of quantum dot barcodes with microfluidics and signal processing for multiplexed high-throughput infectious disease diagnostics. Nano Letter. 2007;7(9):2812–2818. Copyright © 2007 American Chemical Society.

Figure 3

Point-of-care nanodiagnostics for tuberculosis through magnetic barcode assay. Notes: (A) The procedure of the assay including off-chip DNA extraction, asymmetric PCR, target capture, magnetic labeling, and µNMR detection. (B) The illustration of the fluidic cartridge that was used to streamline the assay (scale bar =1 cm). (C) The scanning (scale bar =1 µm) and transmission (scale bar =30 nm, inset) electron microscopy demonstrated that the beads were captured by the membrane filters and labeled with MNPs. Reprinted by permission from Macmillan Publishers Ltd: Nature Communications. Liong M, Hoang A, Chung J, et al. Magnetic barcode assay for genetic detection of pathogens. 2013;4:1752. Copyright 2013. Abbreviations: MNPs, magnetic nanoparticles; NMR, nuclear magnetic resonance; PCR, polymerase chain reaction.

Figure 4

Overview of the cell phone-based point-of-care diagnosis for human immunodeficiency virus and syphilis. Notes: (A) The iPod touch connected to the dongle with a microfluidic cassette. (B) Schematic illustration of dongle with a power-free vacuum generator. (C) Left: The reagent cassette that contains prestored reagents at the top layer and the test cassette at the bottom layer. Right: The flow sequences through test cassette. (D) Comparison of conventional ELISA versus the dongle for the diagnostic test. From Laksanasopin T, Guo T, Nayak S, et al. A smartphone dongle for diagnosis of infectious disease at the point-of-care. Science Translational Medicine. 2015;7(273):273re1. Reprinted with permission from AAAS. Copyright 2015 The American Association for the Advancement of Science. Abbreviations: ELISA, enzyme-linked immunosorbent assay; LEDs, light-emitting diodes.

Figure 5

Paper-based point-of-care nanodiagnostic platform for the detection of YFV, ZEBOV, and DENV using AgNPs for infectious diseases. Notes: (A) Lateral flow strips with CP loaded individually with orange, red, and green AgNPs conjugated to mAbs (from left to right). The size of strip is 20×3 mm. (B) Illustration of the sandwich assay. Limit of detection of (C) YFV NS1, (D) ZEBOV GP, and (E) DENV NS1 using the different AgNP-Abs. Reproduced from Yen C, Puig H, Tam J, et al. Multicolored silver nanoparticles for multiplexed disease diagnostics: distinguishing dengue, yellow fever, and Ebola viruses. Lab Chip. 2015;15:1638–1641. DOI http://dx.doi.org/10.1039/C5LC00055F, with permission of The Royal Society of Chemistry. © Royal Society of Chemistry. Available from: http://dx.doi.org/10.1039/c5lc00055f. Abbreviations: AgNPs, silver nanoparticles; CP, conjugate pads; DENV, dengue virus; GP, glycoprotein; mAbs, monoclonal antibodies; NC, nitrocellulose; NS1, nonstructural protein 1; SP, sample pad; YFV, yellow fever virus; ZEBOV, Ebola virus, Zaire stain.